ZAPAIN

4).

Adults:

The usual dose is one or two capsules every four to six hours as required up to a maximum of 8 capsules in any 24 hour period. Codeine should be used at the lowest effective dose for the shortest period of time. This dose may be taken, up to 4 times a day at intervals of not less than 6 hours.

Maximum daily dose should not exceed 240 mg. The duration of treatment should be limited to 3 days and if no effective pain relief is achieved the patients/carers should be advised to seek the views of a physician. Elderly A reduced dosage may be necessary.

Paediatric population Children aged 16-18 years: 1-2 capsules every 6 hours when necessary up to a maximum of 8 capsules in 24 hours. Children aged 12 – 15 years: 1 capsule every 6 hours when necessary up to a maximum of 4 capsules in 24 hours.

4). Dosage needs to be adjusted according to the severity of pain and the response of the patient. Tolerance to Codeine can develop with continued use. The incidence of unwanted effects is dose related. Doses of Codeine above 60 mg are associated with an increase in unwanted effects.

Method of administration Oral. Treatment goals and discontinuation Before initiating treatment with Zapain, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with codeine, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4). Duration of treatment Zapain should not be used longer than necessary.

Adverse reactions are listed according to MedDRA system organ class and frequency category.

Frequency categories are defined using the following convention:

Uncommon (≥1/1,000 to <1/100) Not known (cannot be estimated from the available data) Reported adverse reactions seem more prominent in ambulatory than non-ambulatory patients and some of these effects may be alleviated if the patient lies down.

4) Nervous system disorders Not known Dizziness, sedation, headache Ear and labyrinth disorders Not known Deafness1 Respiratory thoracic and mediastinal disorders Not known Bronchospasm, dyspnoea Gastro-intestinal Not known Nausea, vomiting, constipation, abdominal disorders pain, pancreatitis2 Hepatobiliary disorders Not known Sphincter of Oddi dysfunction Skin and subcutaneous tissue disorders Not known Pruritus, rash, urticaria General disorders and administration site conditions Uncommon Drug withdrawal syndrome 1Deafness has been reported in patients after long term use of high doses of codeine- paracetamol.

2Drug-induced pancreatitis associated with paracetamol has been reported in literature to be a rare reaction only occurring in patients taking in excess of the recommended doses. Literature reports have also associated cases of pancreatitis with codeine.

4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients. In addition, miosis, visual disturbances, respiratory depression, difficult micturition and urinary retention can occur. Allergic reactions (including skin rash), urticaria and pruritus can occur as reactions to Zapain.

Liver damage in association with therapeutic use of paracetamol has been documented; most cases have occurred in conjunction with chronic alcohol abuse. There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

There have been some reports of blood dyscrasias - thrombocytopenia and agranulocytosis, with the use of paracetamol-containing products, but the causal relationship has not been established. Anaphylaxis, angioedema and toxic epidermal necrolysis have also been associated with the use of paracetamol.

Regular prolonged use of codeine is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is then stopped. Long-term usage of high doses of codeine + paracetamol can be rarely associated with ototoxicity leading to sensorineural hearing loss.

Prolonged use of a pain killer for headaches can make them worse. Drug dependence Repeated use of Zapain can lead to drug dependence, even at therapeutic doses. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

The risk-benefit of continued use should be assessed regularly by the prescriber. Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as Zapain.

Repeated use of Zapain can lead to OUD. A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Zapain may result in overdose and/or death. g. major depression, anxiety and personality disorders).

2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should contact their physician. g. too early requests for refills). This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines).

For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered. The efficacy and safety of Zapain capsules in children below the age of 12 years has not been established and use in such children is contraindicated.

Zapain capsules must be used with caution in debilitated, patients with impaired hepatic or renal function, CNS depression, pre-existing respiratory depression or those with the potential to develop respiratory depression, urethral stricture, and biliary tract disorders (including recent biliary tract surgery).

Care should be observed in administering the product to any patient, whose condition may be exacerbated by opioids, including the elderly, who may be sensitive to their central and gastro-intestinal effects, those on concurrent CNS depressant drugs, those with prostatic hypertrophy, hypothyroidism and those with acute abdominal conditions like inflammatory or obstructive bowel disorders, Addison's disease or myasthenia gravis.

Care should also be observed if prolonged therapy is contemplated. g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring, is recommended.

The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors. CYP2D6 metabolism Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite.

If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses.

These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels. General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite.

In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. 9% Northern European 1%-2% Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. 3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultrarapid or extensive metabolisers in their ability to metabolise codeine to morphine.

Children with compromised respiratory function Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures.

” The hazards of paracetamol overdose are greater in those with non-cirrhotic alcoholic liver disease. Severe liver damage may occur if the maximal daily dose of paracetamol is exceeded or if this product is taken while consuming large amounts of alcohol or with another paracetamol-containing product.

Although paracetamol might logically be presumed to be the best alternative analgesic in patients with aspirin sensitivity, cross reactions have been reported. Patients positively identified with aspirin induced asthma, or […]

1. Children under 12 years of age. Zapain is contraindicated in patients with moderate to severe degrees of renal or hepatic impairment. It is contraindicated in patients for whom opiate medications should not be used, such as patients with acute asthma, obstructive airway disease, respiratory depression, acute alcoholism, head injuries, raised intracranial pressure, after biliary surgery and patients suffering from diarrhoea of any cause.

6) In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.